Investigation of the Role of H2S in the Beneficial Effects of Osthole on Erectile Function
Project no. 22681 · Status: Kapanmış · 2021
Summary
<p>Erectile function is a neurovascular process facilitating erection by relaxing penile tissue. Erectile dysfunction(ED) is an impairment in achieving/maintaining an erection. For PDE-5 inhibitors used in treatment to be effective, there must be no dysfunction in endothelium/NO production. It has been reported that PDE-5 inhibitors are ineffective in 30–40% of ED patients. This highlights the significance of using agents for ED treatment that can act independently of endothelial functions. Hydrogen sulfide(H2S), a gasotransmitter enhancing erectile function through endothelium-independent mechanisms, is synthesized from L-cysteine by cystathionine-γ-lyase(CSE), cystathionine-β-synthase(CBS), and 3-mercaptopyruvate-sulfurtransferase(3-MST) enzymes. Osthole, a natural coumarin, shows beneficial effects on the cardiovascular system and relaxes penile tissue more effectively than papaverine. Our literature review revealed that the pharmacological activities of osthole are mediated through mechanisms shared with H2S. This project aimed to investigate, for the first time, the role of H2S in the beneficial effects of osthole on erectile function. Isolated organ bath, real-time H2S measurement, Western blot experiments were conducted using mouse corpus cavernosum. Osthole-induced relaxations were inhibited by the H2S synthesis inhibitor aminooxyacetic acid(AOAA),L-NAME,ODQ,glibenclamide. Osthole increased L-cysteine-, Na2S-, acetylcholine-, and sodium nitroprusside-induced relaxations. These enhancements are inhibited by AOAA. Osthole increased L-cysteine-induced H2S synthesis, CSE and CBS expressions, reflecting on enzyme activities. These results indicate that osthole promotes relaxation by increasing H2S synthesis, contributing to its NO-mediated relaxing effect, and implicating sGC, KATP channels in osthole-induced relaxations. The potential use of osthole in treating endothelial dysfunction-related ED and diseases with reduced NO/H2S bioavailability such as hypertension, diabetes has been elucidated.</p>